AGE

, 36:9635

WNT3A gene polymorphisms are associated with bone mineral density variation in postmenopausal mestizo women of an urban Mexican population: findings of a pathway-based high-density single nucleotide screening

  • Rafael Velázquez-Cruz
  • Humberto García-Ortiz
  • Manuel Castillejos-López
  • Manuel Quiterio
  • Margarita Valdés-Flores
  • Lorena Orozco
  • Teresa Villarreal-Molina
  • Jorge Salmerón
Article

DOI: 10.1007/s11357-014-9635-2

Cite this article as:
Velázquez-Cruz, R., García-Ortiz, H., Castillejos-López, M. et al. AGE (2014) 36: 9635. doi:10.1007/s11357-014-9635-2

Abstract

Osteoporosis (OP) is a common skeletal disorder characterized by low bone mineral density (BMD) and is a common health problem in Mexico. To date, few genes affecting BMD variation in the Mexican population have been identified. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) located in genes of the Wnt pathway with BMD variation at various skeletal sites in a cohort of postmenopausal Mexican women. A total of 121 SNPs in or near 15 Wnt signaling pathway genes and 96 ancestry informative markers were genotyped in 425 postmenopausal women using the Illumina GoldenGate microarray SNP genotyping method. BMD was measured by dual-energy X-ray absorptiometry in total hip, femoral neck, Ward’s triangle, and lumbar spine. Associations were tested by linear regression for quantitative traits adjusting for possible confounding factors. SNP rs752107 in WNT3A was strongly associated with decreased total hip BMD showing the highest significance under the recessive model (P = 0.00012). This SNP is predicted to disrupt a binding site for microRNA-149. In addition, a polymorphism of the Wnt antagonist DKK2 was associated with BMD in femoral neck under a recessive model (P = 0.009). Several LRP4, LRP5, and LRP6 gene variants showed site-specific associations with BMD. In conclusion, this is the first report associating Wnt pathway gene variants with BMD in the Mexican population.

Keywords

Bone mineral densityPolymorphismsWnt pathwayPostmenopausal Mexican women

Supplementary material

11357_2014_9635_MOESM1_ESM.doc (306 kb)
ESM 1(DOC 305 kb)

Copyright information

© American Aging Association 2014

Authors and Affiliations

  • Rafael Velázquez-Cruz
    • 1
  • Humberto García-Ortiz
    • 2
  • Manuel Castillejos-López
    • 3
  • Manuel Quiterio
    • 4
  • Margarita Valdés-Flores
    • 5
  • Lorena Orozco
    • 2
  • Teresa Villarreal-Molina
    • 6
  • Jorge Salmerón
    • 7
  1. 1.Laboratorio de Genómica del Metabolismo ÓseoInstituto Nacional de Medicina GenómicaMéxicoMéxico
  2. 2.Laboratorio de Inmunogenómica y Enfermedades MetabolicasInstituto Nacional de Medicina GenómicaMéxicoMéxico
  3. 3.Unidad de Vigilancia Epidemiológica HospitalariaInstituto Nacional de Enfermedades RespiratoriasMéxicoMéxico
  4. 4.Centro de Investigación en Salud PoblacionalInstituto Nacional de salud PúblicaCuernavacaMéxico
  5. 5.Servicio de GenéticaInstituto Nacional de RehabilitaciónMéxicoMéxico
  6. 6.Laboratorio de Enfermedades CardiovascularesInstituto Nacional de Medicina GenómicaMéxicoMéxico
  7. 7.Unidad de Investigación Epidemiológica y en Servicios de SaludInstituto Mexicano del Seguro SocialCuernavacaMéxico